The mechanism of the inhibition of glucuronidation by long-chain fatty
acyl-CoAs was studied in rat liver microsomal membranes and in isolat
ed hepatocytes. Palmitoyl and oleoyl-CoA did not affect p-nitrophenol
UDP-glucuronosyltransferase activity in native microsomes but were inh
ibitory in permeabilised vesicles. The extent of inhibition was depend
ent on the effectiveness of permeabilisation and was constant in time
in fully permeabilised microsomes. Fatty acyl-CoAs mobilised calcium f
rom calcium-loaded microsomes. Elevation of the intracellular acyl-CoA
level by the addition oi palmitate or oleate inhibited that glucuroni
dation of p-nitrophenol in isolated hepatocytes. This effect could be
abolished by emptying the intracellular calcium stores. Therefore, it
is concluded that fatty acyl-CoAs inhibit glucuronidation indirectly,
presumably via calcium mobilisation.